Complications of Sickle Cell Disease may potentially be treated by the use of haptoglobin to bind and remove free hemoglobin from the circulation. Free hemoglobin causes oxidative stress and attendant vascular and tissue complications. Haptoglobin binding of free hemoglobin helps prevent entry of free hemoglobin into the kidney and to pass through the vascular endothelium. The development of innovative methodologies to bind and remove free hemoglobin from the circulation may provide a novel therapeutic approach for the management of complications of Sickle Cell Disease.